Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Objective To explore the influencing factors of physical activity behavior change in lung cancer patients and provide a basis for developing targeted intervention programs.Methods A descriptive qualitative research method was employed.Using purposive sampling,18 lung cancer pa-tients and 10 healthcare professionals were selected for semi-structured interviews from October to De-cember 2023.The health action process approach(HAPA)theory was used as the framework,and directed content analysis was applied to analyze the data.Results The barriers to physical activity behavior change in lung cancer patients were distilled into six themes:insufficient risk perception,negative outcome expectations,self-doubt and behavior avoidance tendencies,challenges in persist-ence and risk of interruption,lack of behavioral intention and demand,and absence of action and coping plans.The facilitating factors were divided into six themes:perception of the potential hazards of insufficient physical activity,perception of the health benefits of physical activity,cultivation and development of self-efficacy,stimulation of motivation for activity,formulation of differentiated activity plans,and formulation of adaptive coping plans.Conclusion Physical activity behavior in lung cancer patients is influenced by multiple factors.Targeted intervention strategies can be developed based on the HAPA theory to promote physical activity behavior change and improve physical activity levels.

Objective:To analyze the occupational disease hazards in stone processing enterprises in Weihai City to provide scientific basis for occupational disease prevention.Methods:From January 2021 to December 2022, 107 stone processing enterprises in Weihai City were selected to collect the detection status of occupational hazard factors in the workplace through on-site investigation and on-site monitoring of occupational hazard factors. The diagnostic reports on occupational diseases and suspected occupational diseases of 780 workers were collected through the Occupational Diseases and Hazard Factors Monitoring Information System of the Chinese Center for Disease Control and Prevention, the occupational health monitoring files of the occupational health examination institutions and the information data of the occupational disease diagnosis institutions. The differences between the measurement data were analyzed by Chi-square test or Fisher exact probability method.Results:107 stone processing enterprises were mainly focused on granite processing, and the average free silica content in granite was 32.92% (12.78%-47.84%). The over-standard rate of silica dust was 0.31% (6/1920), and the over-standard rate of noise was 86.20% (1324/1536). Among them, the noise intensity of cutting position was the highest[120.5 dB (A) ]. The over-standard rates of noise in cutting, water grinding, dry grinding (polishing) and material preparation (forklift transportation) were 98.05%, 89.55%, 70.00% and 42.62%, respectively, and the differences were statistically significant ( P<0.05). Among 780 workers, 31 cases (3.97%) of suspected silicosis were detected, and 13 cases (1.67%) were diagnosed with silicosis. 51 cases (6.54%) of suspected occupational noise deafness were detected, and 11 cases (1.41%) were diagnosed with occupational noise deafness. Conclusion:Silicon dust and noise in some positions of stone processing enterprises in Weihai City exceed the standard, and supervision should be strengthened, prevention and control measures should be implemented to protect the occupational health of workers.

Objective:To analyze the occupational disease hazards in stone processing enterprises in Weihai City to provide scientific basis for occupational disease prevention.Methods:From January 2021 to December 2022, 107 stone processing enterprises in Weihai City were selected to collect the detection status of occupational hazard factors in the workplace through on-site investigation and on-site monitoring of occupational hazard factors. The diagnostic reports on occupational diseases and suspected occupational diseases of 780 workers were collected through the Occupational Diseases and Hazard Factors Monitoring Information System of the Chinese Center for Disease Control and Prevention, the occupational health monitoring files of the occupational health examination institutions and the information data of the occupational disease diagnosis institutions. The differences between the measurement data were analyzed by Chi-square test or Fisher exact probability method.Results:107 stone processing enterprises were mainly focused on granite processing, and the average free silica content in granite was 32.92% (12.78%-47.84%). The over-standard rate of silica dust was 0.31% (6/1920), and the over-standard rate of noise was 86.20% (1324/1536). Among them, the noise intensity of cutting position was the highest[120.5 dB (A) ]. The over-standard rates of noise in cutting, water grinding, dry grinding (polishing) and material preparation (forklift transportation) were 98.05%, 89.55%, 70.00% and 42.62%, respectively, and the differences were statistically significant ( P<0.05). Among 780 workers, 31 cases (3.97%) of suspected silicosis were detected, and 13 cases (1.67%) were diagnosed with silicosis. 51 cases (6.54%) of suspected occupational noise deafness were detected, and 11 cases (1.41%) were diagnosed with occupational noise deafness. Conclusion:Silicon dust and noise in some positions of stone processing enterprises in Weihai City exceed the standard, and supervision should be strengthened, prevention and control measures should be implemented to protect the occupational health of workers.

Objective:To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC).Methods:916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ2 test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results:There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ2 = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ2 = 4.519, P = 0.029; 13.2% vs. 26.2%, χ2 = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group ( P = 0.38). Conclusion:Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.

OBJECTIVE：To establish quantitative e valuation system of the prophylactic use of antibiotics in orthopedic type Ⅰ incision surgery ，and to provide reference for evaluating the rational prevention use of antibiotics in this type surgery scientifically. METHODS：Based on the Guidelines of Clinical Use of Antimicrobial Agents （2015 edition），drug instructions ，related guidelines and references ，experts from relevant departments jointly discussed and formulated the evaluation criteria for the rationality of the use of antibiotics in type Ⅰ incision in orthopedic surgery. AHP method was used to assign the weights for various indexes of evaluation criteria ；TOPSIS method was used to retrospectively analyze and evaluate the rationality of 120 cases of type Ⅰ incision surgery from 3 orthopedic departments in Peking University People ’s Hospital during Sept. 1st-30th，2019. RESULTS ：Established evaluation system included 4 primary indicators （medication indication ，usage and dosage ，medication timing ，other factors ）and 12 secondary indicators. Among the secondary indicators ，indications，drug selection and timing of preoperative administration were the most important （weights were 0.209，0.140，0.117）. Among 120 cases，30.83％ of drug use were reasonable ，47.50％ were basically reasonable and 21.67％ were unreasonable. Evaluation results obtained by AHP-TOPSIS were consistent with the actual situation. CONCLUSIONS ：The rationality evaluation method of prophylactic use of antibiotics in type Ⅰ incision surgery based on AHP-TOPSIS method can quantitatively evaluate the rationality of drug use by combining multiple indicators. The method is feasible ，operable，and the evaluation results can be quantified ，which has a wide range of application.

Objective To study the effect of hyperbaric oxygen (HBO) on the proliferation and differentiation of neural stem cells (NSCs) in rats after middle cerebral artery occlusion (MCAO).Methods Seventy-two adult,male,Sprague-Dawley rats were randomly divided into a control (CON) group,a hyperbaric air (HBA) group,a normobaric oxygen (NBO) group and a hyperbaric oxygen (HBO) group.All were subjected to MCAO.Rats in the CON group did not receive any treatment; those in the other groups were treated with HBA,NBO or HBO daily beginning 2 hours after the operation.Western blotting was applied to detect the expression of nestin,MAP2 and GFAP at 2,3,7 and 14 days after the MCAO.Results The expression of nestin in the HBO group was significantly higher than in the other groups on the 3rd,7th and 14th days.It peaked at day 3 but remained high until day 14.Similarly,expression of MAP2 was significantly higher than in the other groups at least until day 14.GFAP expression was significantly lower than in the other groups.Conclusion HBO can increase neural stem cell proliferation and neuronal differentiation,and inhibit the proliferation of astrocytes.